|Year : 2019 | Volume
| Issue : 4 | Page : 801-806
Preliminary investigation of computed tomography-guided iodine-125 seed implantation treatment efficacy in patients with iliac lymph nodes metastases
Hongtao Zhang, Huimin Yu, Yansong Liang, Zeyang Wang, Xuemin Di, Lijuan Zhang, Jinxin Zhang, Zezhou Liu, Aixia Sui, Juan Wang
Department of Oncology, The Hebei General Hospital, Shijiazhuang, China
|Date of Web Publication||14-Aug-2019|
Department of Oncology, The Hebei General Hospital, Shijiazhuang 050051
Source of Support: None, Conflict of Interest: None
Objectives: The objective of this study is to assess the technical feasibility, safety, and efficacy of computed tomography (CT)-guided iodine-125 (125 I) seed implantation to treat malignant iliac lymph node metastases.
Materials and Methods: In this retrospective study, 11 patients with a total of 11 iliac lymph node metastases were implanted with 125 I seeds (14.8–25.9 MBq) under CT-guidance, both the seed quantity and distribution were measured with a computerized treatment planning system. Treatment effects and adverse events were evaluated.
Results: 125 I seeds were successfully implanted in all patients, and the minimum peripheral dose of seeds was ranged from 30 to 110 Gy (median of 75 Gy). The median follow-up period was 11 months (ranged 3–39 months). Follow-up at 2 months after implantation revealed partial response in eight patients, stable disease in two patients, and progressive disease in one patient. The overall response rate and the local tumor control rate at 2 months were 72.73% and 90.91%, respectively. The rates of refractory pain and leg edema relief were 100% and 50% within 2 weeks after treatment, respectively. Survival rate at 1 year was 45.45%. No peri-interventional mortality or major complication was observed.
Conclusion: 125 I seed implantation was a safe and effective technique for minimally invasive treatment for iliac lymph node malignant metastasis.
Keywords: Brachytherapy, iliac lymph node metastasis, interstitial implantation, radioactive iodine-125 seed
|How to cite this article:|
Zhang H, Yu H, Liang Y, Wang Z, Di X, Zhang L, Zhang J, Liu Z, Sui A, Wang J. Preliminary investigation of computed tomography-guided iodine-125 seed implantation treatment efficacy in patients with iliac lymph nodes metastases. J Can Res Ther 2019;15:801-6
|How to cite this URL:|
Zhang H, Yu H, Liang Y, Wang Z, Di X, Zhang L, Zhang J, Liu Z, Sui A, Wang J. Preliminary investigation of computed tomography-guided iodine-125 seed implantation treatment efficacy in patients with iliac lymph nodes metastases. J Can Res Ther [serial online] 2019 [cited 2019 Aug 17];15:801-6. Available from: http://www.cancerjournal.net/text.asp?2019/15/4/801/264293
| > Introduction|| |
Abdominal and pelvic malignancy often leads to retroperitoneal lymph node metastases which include nodal lesions located adjacent to the ilium. These lesions are widely distributed, deeply seeded, and often surrounded by multiple blood vessels and peripheral nerves. Enlarged lymph nodes generally lead to severe pain and edema, which severely compromised the patients' quality of life. However, systematic resection of all involved lymph nodes has been generally difficult. Chemotherapy seems ineffective for eradicating tumor deposits in the lymph nodes, suggesting that lymph nodes may function as a pharmacological sanctuary. Management of bulky lymph node metastases has been particularly challenging, especially for patients with multiple comorbidities. It would be further complex considering the patients' general conditions, treatment history, and their tolerance to daily treatment dose., Under such circumstances, alternative management for recurrent lymph node metastasis is urgently required, which has not yet been established.
Currently, external beam radiation therapy (EBRT) is the standard procedure for lymph node metastase management. It has been often regarded as an effective palliative treatment. However, EBRT requires daily dose treatment, each of which involves realignment of the beams according to the original computed tomography (CT) scans. These alignments may bring on unnecessary damage to normal organs because of alignment errors. In addition, although readministering the EBRT for recurrent lymph nodes has been reported to make similar effectiveness on local tumor control and pain reduction, compared to that of the initial irradiation,, it has also been associated with significant incidence of late toxicity attribute to accumulated dose in at-risk organs, such as the small intestine., Proton therapy could deliver very high doses to fixed retroperitoneal nodal metastasis without much dose to surrounding structures; however, its clinical application has been limited by the relative high cost. Percutaneous CT-guided radioactive iodine-125 (125 I) seed implantation has the advantage of delivering dose to moving organs without the uncertainty of dose delivery by externally applied radiotherapy; in addition, it has been more cost-effective compared to the proton therapy. Moreover, seed implantation is especially useful for previously radiated areas with EBRT, and encouraging results have been obtained from its applications on treating metastatic lymph nodes.,, However, the efficacy of 125 I seed implantation treatment has not been evaluated for patients with iliac lymph node metastases. Thus, we preliminarily studied the application of CT-guided 125 I seed implantation on treating isolated iliac lymph node metastases.
| > Materials and Methods|| |
This retrospective analysis included 11 patients with isolated metastatic iliac lymph nodes treated with CT-guided 125 I seeds in our hospital during February 2006 and September 2014 [Table 1]. All patients received prior treatment, including radical surgery, chemotherapy and/or radiation therapy for different solid cancers, and all of them, had recurrent iliac lymph node metastases. The diagnosis of iliac lymph node metastasis (Common lliac lymph Nodes, external iliac lymph nodes, and internal iliac lymph nodes) was conducted based on the results of radiological and pathological examinations. Enrolled patients had difficulties in complete metastatic excisions, including poor general conditions and intolerance of or unwilling to receive postoperative radiation therapy. For all enrolled patients, iliac metastatic lymph nodes have been confirmed with CT, magnetic resonance imaging, or positron emission tomography (PET)-CT. Their Eastern Cooperative Oncology Group (ECOG) performance scores were three or less, with an expected lifespan of 3 months or longer. Patients had neutrophil leukocyte count of >3×109/L, platelets of >100 × 1012/L, and hemoglobin of >90 g/L in peripheral blood. The heart, lung, and other major organs of all the patients were normal. Patients with severe heart, liver, lung, kidney dysfunction; severe coagulation disorders; poor general conditions or cachexia; or abundant ascites were excluded from this procedure. All patients were informed of potential benefits and risks, and signed written consent was obtained from each patient before implantation therapy. The study protocol was reviewed and approved by the Ethics Committee of our institute.
Mick 200-TPV applicator and 18G implantation needles were purchased from Mick Radio-Nuclear Instruments Inc. (Mt Verson, NY).125 I sealed seed sources (model 6711-99) were purchased from XinKe Pharmaceutical Ltd (Shanghai, China). Seed diameter and length were 0.8 and 4.5 mm, respectively.125 I seeds were sealed in titanium capsules (wall thickness of 0.05 mm) with an activity of 14.8–25.9 MBq and a half-life of 59.6 days.
Computed tomography-guided, iodine-125 seed implantation procedures
Discovery PET/CT Elite CT scanner (GE Medical Systems LLC) was applied to locate lesion and to guide seeds implantation. An 18G implantation needle was applied for the implantation of 125 I seeds. Preprocedure computerized treatment planning was performed on a Treatment Planning System (TPS, Prowess 3D System, Version 3.02; Prowess Inc., Concord CA). The radioactivity of the 125 I seeds was ranged from 14.8 to 25.9 MBq. According to the CT images, the gross tumor volume (GTV) and areas at risk of subclinical disease on each transverse image were outlined. The planning target volume (PTV) included the entire GTV with a margin of 5 mm. The D90 (indicating the dose received by 90% of the PTV) of 125 I seeds were calculated with TPS.
The patients fasted for 2 h and were administered with sedatives and local anesthesia before the CT-guided brachytherapy procedures. The skin at the needle entry site was prepared and draped in a sterile fashion. Based on the preimplant treatment plan, 18G implantation needles were placed 1.0 cm apart with each other in a parallel array within the PTV. Precautions were taken to avoid puncturing the large blood vessels, neural structures, and important organs. The depth and angel of the implanted needles were monitored by repeated CT imaging and adjusted when necessary. After placing the needles,125 I seeds were released every 0.5 cm–1 cm apart with the gradual withdrawal of the needles. The seeds were loaded utilizing a modified peripheral approach in which fewer central seeds and more peripheral seeds were implanted according to the preplanning. Puncture sites were bandaged and compressed to reach hemostasis after the procedure. After the implantation, patients were administered with prophylactic antibiotics for 3 days and tramadol hydrochloride injection when necessary.
Postoperative dosimetric measurements were routinely performed for all patients within 2 days after the procedure. The 125 I seeds were identified on the CT images by manual selection. Isodose curves for each slice and dose-volume histograms of the target were generated. The actuarial median number of the implanted 125 I seeds was 80 [ranged from 10 to 295; [Table 2]. The specific activity of 125 I seeds ranged from 14.8 to 25.9 MBq (median of 22.2). The postplan evaluation indicated that the actuarial D90 was ranged from 30 to 110 Gy (median of 75 Gy).
The surgeon performed 125 I implantation in a specially designed operating room. At the time of the procedure, all medical personnel wore lead gloves, hats, and other protective equipment. The surroundings were surveyed to detect any ray dosage to prevent missing seeds or other problems.
Follow-up and evaluation criteria
Vital signs of all patients were monitored for 24 h after implantation. Any changes from the symptoms observed at presentation were recorded. A clinical examination and CT imaging were performed at 2 months after the procedure to evaluate the therapeutic effectiveness. Based on these examinations, the tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors. Pain evaluation was carried out before seed implantation, on a daily basis during the immediate postoperation period, and on a weekly basis when the pain level was stabilized.
Tumor response evaluation
Tumor responses to 125 I seed implantation therapy were assessed according to the World Health Organization Response Evaluation Criteria in Solid Tumors (RECIST, Version 2000)., In brief, complete response (CR) was defined as the disappearance of all target lesions; radiological examine showed no lesion or nodal can only be faintly seen; partial response (PR) was defined as size of the lesion (i.e., the longest dimension multiplied by maximal upright dimension) was decreased by >50%; stable disease (SD) was defined as the size of the lesion was decreased by <50% or increased by <25%, which was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD was defined as the size of the lesion was increased by >25% or the appearance of one or more new lesions. Response rate and local tumor control rate were determined with following formula: response rate = (CR + PR)/case number and local control rate = (CR + PR + SD)/case number.
Pain scale evaluation
Numerical rating scale was applied to measure the level of pain, with 0–10 representing various pain levels: 0 indicated no pain at all and 10 indicated the worst pain imaginable. Patients were asked to rate their pain intensity and choose the numeric number based on their individual feelings.
The complications were scored with the radiation therapy oncology group acute radiation morbidity scoring criteria (1995). Major complications, i.e., fever, hemorrhage, bone marrow suppression, liver/kidney dysfunction, skin/mucosal reaction, or others were observed during our follow-up period.125 I seeds locations were monitored with CT scans.
SPSS 13.0 software (SPSS, IL, USA) was applied for statistical analysis. The change in lymph nodes size and pain scales before and after 125 I seeds implantation were compared with nonparametric test. P < 0.05 was considered statistically significant.
| > Results|| |
Data of patients were listed [Table 2]. The lymph nodes of five patients (45.45%) were >6 cm.
Responses to iodine-125 seed implantation treatment
Overall, 11 isolated iliac lymph node metastases in 11 patients were treated with 125 I seed implantation [Table 2] with a follow-up period of 3–39 months (median follow-up period was 11 months). [Figure 1] showed CT images for one patient before and after treatment.
|Figure 1: (a) Patient two, bladder cancer Grade II–III, Stage IV, with left iliac lymph node metastasis before implantation. (b) Dose distribution immediately after implantation (colored lines represent isodose curves). (c) Two months after seeds implantation. (d) Twenty months after seeds implantation|
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CT images at 2 months postimplantation indicated PR in eight patients, SD in two patients and PD in one patient. Lymph node average sizes were decreased from 42.4 ± 37.4 cm 2 before treatment to 26.3 ± 28.5 cm 2 posttreatment (P < 0.05). At 2 months posttreatment, average response rate and local tumor control rate were 72.7 and 90.9%, respectively. Average response rate for lymph nodes smaller than and equal to 6 cm was 83.3%, which was significantly higher than that of for lymph nodes larger than 6 cm (60%). Average response rates for the five patients who received D90 <75 Gy was 60% (including 3 PR, 1 SD, and 1 PD). In contrast, the average response rate was 83.3% (5 PR and 1 SD) for six patients who received D90 ≥75 Gy. One-year survival was 45.5%, and four patients died from metastatic lesions, three patients suffered from multiple organ failure, and four patients survived until the end of the follow-up.
Palliative effects of iodine-125 implantation
For the 11 enrolled patients, refractory pain was observed in eight before seed implantation, and pain was resolved significantly in all eight patients within 14 days postimplantation. Pain scores were decreased from 4.3 ± 4.5 before treatment to 2.0 ± 2.5 at 2 months after treatment (P < 0.05). Of the 11 patients, leg edema was observed in two cases before seed implantation, which was resolved in one patient within 14 days postimplantation.
No major complication (fever, hemorrhage, bone marrow suppression, liver/kidney dysfunction, skin/mucosal radiation reaction, radiation enteritis, or cystitis) was observed during our follow-up period. No seeds migrated to other tissues or organs.
| > Discussion|| |
Retroperitoneal lymph nodes are usually deeply seeded in the abdomen, which are also adjacent to the abdominal aorta and inferior vena cava. In addition, these lymph nodes may infiltrate into surrounding organs or neural structures. Although the frequency of associated surgical complications has decreased recently, it still approached 10%., Even if nodal lesions could be completely removed, for the recurrent tumors, reoperation may be still problematic due to scar and adhesive tissue, ambiguously defined lesions, and/or anatomic variations caused by previous surgery. In these patients, systemic or intraperitoneal chemotherapy, palliative radiation therapy, drug treatment, or neurolytic celiac plexus blockade for pain management have been all associated with severe adverse effects and offered only limited benefits for prolonging survival.,,
Recently, CT-guided 125 I implantation has been applied to treat malignant retroperitoneal lymph node metastases and the clinical outcomes have been promising. Yao's group  utilized CT-guided coaxial 125 I seed implantation for treating retroperitoneal lymph node metastasis. Lymph nodes were ranged from 2.2 cm to 6.3 cm, and the response rate (CR + PR) at 6 months postimplantation was 90.5%. Bloating and abdominal pain were significantly improved, and no complication was observed. McLean and Twomey  investigated the treatment efficacy of CT-guided 125 I implantation in 33 patients with a total of 50 retroperitoneal lymph node metastases and they reported a response rate (CR + PR) at 1-month postimplantation of 90.0% and pain relieved in 83.3% of patients. Wang et al., treated 25 patients with retroperitoneal lymph node metastases utilizing CT-guided 125 I implantation (average lymph node sizes of 3.0 ± 1.5 cm), and the reported CR + PR at 2 months postimplantation was 80%. Our work indicated a lower overall effect rate at 2 months (72.7%), which may be explained by the recurrent nature of the lesions involved in this study and the relatively larger lymph nodes in our patients (average lymph node length of 6.7 ± 2.9 cm). According to the Wang's  report on 17 patients with a total of 23 recurrent cervical lymphatic metastases, after EBRT, the control rate at 6 months was 65.2%; CR + PR for lymph nodes less than 4 cm (n = 10) and greater than 4 cm (n = 1) were 90%, and 46%, respectively, and these group differences were statistically significant. In our work, the response rate at 2 months postimplantation for lymph nodes <6 cm was significantly higher than that of for lymph node >6 cm. Therefore, size of lymph nodes might also contribute to treatment efficacy.
The treatment efficacy of 125 I implantation therapy could be affected by radiation dose. In this study, most patients' D90 were less than PD because the seeds were implanted under CT guidance without a template. The preplan cannot be applied very well by the operators. In 2015, our team first involved 3D printed template to guide the needle, the dose distribution was consistent with preplan. Chinese experts already published consensus about 3D printed template-guided brachytherapy in 2017. If 3D printed template was applied in this study, the result might be better. We observed a response rate for the five patients who received D90 <75 Gy that was less compared to that of for six patients who received D90 >75 Gy. Yin's group  suggested that radiation doses cannot be <60–75 Gy for controlling tumor growth and Wang et al. reported that the external beam radiation D90 must be 80–90 Gy, or as high as 100 Gy for eradicating adenomas larger than 5 cm., Our results have been consistent with literature that D90 was critical for determining 125 I implantation treatment efficacy and that clinical outcomes would be improved with D90 >75 Gy. The patients analyzed in the present study received prior comprehensive treatments including radical surgery, chemotherapy and/or radiation therapy for various solid cancers. All of them had recurrent iliac lymph node metastases. They could not either tolerate reoperation or suffer from unsatisfactory clinical outcomes from EBRT and/or chemotherapy. For patients with metastatic lymphadenopathy, pain was common thus decreasing patients' quality of life. Underlying causes or mechanisms of such pain may be related to surrounding plexus invasion, and/or damage or compression of afferent nerve fibers. In our study, the pain was relieved by 125 I seed implantation in all patients. Wang's group  retrospectively analyzed treatment effects of 125 I implantation for malignant lymph node metastases in 27 cases; the pain was relieved in six of eight patients, and patients' life quality was improved significantly. Compared with morphine and other conventional analgesics,125 I implantation was associated with less nausea, constipation, lethargy, vomiting or respiratory depression, and other complications. After 125 I seed implantation, edema was reduced significantly in one patient but was not relieved in another patient due to the enlarged lymph nodes compressing axillary lymph and blood vessels.
This was a retrospective study involving 11 patients. One major limitation of this study has been the retrospective design and small sample size, leading to the reduced power of the study. Another limitation was that these patients either had late stage or recurrent cancer, and the general conditions were poor for all of them. They also failed to respond to other therapies and therefore had to receive 125 I seed implantation. As a result, the procedure described here may not be applicable to other patients with varied clinical indications. In addition,125 I seed implantation guidelines for specific seed activity and the optimal minimum peripheral dose has not been deduced here due to the small sample size. Future prospective study with more stringent design and larger sample size is required.
| > Conclusion|| |
CT-guided radioactive 125 I seed implantation offered an alternative radiation treatment for local tumor control and palliative pain relief without severe complications, which may be a safe, effective, and relatively uncomplicated option for treating remnant and recurrent malignant lymph node metastases.
Financial support and sponsorship
This work was financially supported by Hebei Province Health Department (20130412).
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Okamoto Y, Murakami M, Yoden E, Sasaki R, Okuno Y, Nakajima T, et al.
Reirradiation for locally recurrent lung cancer previously treated with radiation therapy. Int J Radiat Oncol Biol Phys 2002;52:390-6.
Burghardt E, Girardi F, Lahousen M, Tamussino K, Stettner H. Patterns of pelvic and paraaortic lymph node involvement in ovarian cancer. Gynecol Oncol 1991;40:103-6.
Wu SX, Chua DT, Deng ML, Zhao C, Li FY, Sham JS, et al.
Outcome of fractionated stereotactic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2007;69:761-9.
Bogusevicius A. Analysis of the outcome of the treatment of small bowel obstruction and factors which determine the outcome (10-year experience at the Kaunas medical university clinic). Medicina (Kaunas) 2002;38:289-95.
Salama JK, Vokes EE, Chmura SJ, Milano MT, Kao J, Stenson KM, et al.
Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2006;64:382-91.
Wang Z, Lu J, Gong J, Zhang L, Xu Y, Song S, et al.
CT-guided radioactive 125
I seed implantation therapy of symptomatic retroperitoneal lymph node metastases. Cardiovasc Intervent Radiol 2014;37:125-31.
Kwong EW, Huh SH, Nobler MP, Smith HS. Intra-operative iodine-125 prostatic implant following bilateral pelvic lymphadenectomy. Int J Radiat Oncol Biol Phys 1984;10:665-70.
Bull1 Sogani PC, DeCosse JJ Jr., Montie J, Whitmore WF Jr., Grabstald H, Hilaris BS, et al.
Carcinoma of the prostate: Treatment with pelvic lymphadenectomy and iodine-125 implants. Clin Bull 1979;9:24-31.
Howard JH, Thompson JF, Mozzillo N, Nieweg OE, Hoekstra HJ, Roses DF, et al.
Metastasectomy for distant metastatic melanoma: Analysis of data from the first multicenter selective lymphadenectomy trial (MSLT-I). Ann Surg Oncol 2012;19:2547-55.
Ebara S, Katayama N, Tanimoto R, Edamura K, Nose H, Manabe D, et al.
Iodine-125 seed implantation (permanent brachytherapy) for clinically localized prostate cancer. Acta Med Okayama 2008;62:9-13.
Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341-6.
Alldinger I, Yang Q, Pilarsky C, Saeger HD, Knoefel WT, Peiper M, et al.
Retroperitoneal soft tissue sarcomas: Prognosis and treatment of primary and recurrent disease in 117 patients. Anticancer Res 2006;26:1577-81.
Heidenreich A, Albers P, Hartmann M, Kliesch S, Kohrmann KU, Krege S, et al.
Complications of primary nerve sparing retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell tumors of the testis: Experience of the German testicular cancer study group. J Urol 2003;169:1710-4.
Yunfeng Z, Guiwen C, Houfa N, Xinjiang C, Hui X, Jinlong H, et al
. Iodine-125 seed implantation for retroperitoneal lymph node metastases treatment. J Med Imaging 2013;9:1430-3.
Bhatnagar S, Gupta M. Evidence-based clinical practice guidelines for interventional pain management in cancer pain. Indian J Palliat Care 2015;21:137-47.
] [Full text]
McLean S, Twomey F. Methods of rotation from another strong opioid to methadone for the management of cancer pain: A systematic review of the available evidence. J Pain Symptom Manage 2015;50:248-590.
Hongxiang Y, Gensheng C, Lei X, Qun Z, Hongbo C, Ye C, et al
. CT-guide coaxial 125I seeds implantation for the treatment of retroperitoneal lymph node metastasis: Analysis of 21 cases. J Intervent Radiol 2014;23:42-5.
Juan W, Meiling S, Hongtao Z, Fulong T, Aixia S, Haishui X. Radioactive 125I seed implantation for the treatment of recurrent cervical lymphatic metastases after radiotherapy: Preliminary results in 17 cases. J Intervent Radiol 2014;23:784-7.
Hongtao Z, Xuemin D, Huimin Y, Zeyang W, Lijuan Z, Jinxin Z, et al.
Dosimetry study of three-dimensional print template-guided precision 125
I seed implantation. J Cancer Res Ther 2016;12:C159-65.
Wang J, Zhang F, Guo J, Chai S, Zheng G, Zhang K, et al.
Expert consensus workshop report: Guideline for three-dimensional printing template-assisted computed tomography-guided 125I seeds interstitial implantation brachytherapy. J Cancer Res Ther 2017;13:607-12.
Weibo Y, Zihao Y, Guozhen X, Yimin H. Radiation Oncology. 4th
ed. Bei Jing; China Union Medical University Press; 2008.
Wang JJ, Yuan HS, Li JN, Jiang WJ, Jiang YL, Tian SQ, et al.
Interstitial permanent implantation of 125
I seeds as salvage therapy for re-recurrent rectal carcinoma. Int J Colorectal Dis 2009;24:391-9.
Jianhua W, Changjing Z, Chengwei S, Xiaolong M, Jian Z, Jianming T. CT-guided 125
I brachytherapy for abdominal lymph node metastases. J Intervent Radiol 2011;20:877-81.
[Table 1], [Table 2]